1. Field of the Invention
Hypersensitive individuals undergo an altered state as a result of contact with the antigens from an allergen leading to the formation of antibodies thereto. Subsequent contact with one of those antigens or a structurally similar substance can evoke in an allergic individual a pathological reaction, due to the presence of antibodies. When these individuals inhale or ingest the offending antigen, a prominent manifestation includes bronchial asthma.
Allergic responses are involved with the production within an individual of a type of tissue-sensitizing IgE antibody called a reagin. These IgE antibodies have a high affinity for receptors on cells present in various body tissues. The receptors are on mast cells which are found in close association with capillaries in connective tissues throughout the body and on basophilic leukocytes (blood cells). Mast cells and basophils contain a high content of pharmacologically-active mediators or spasmogens, such as histamine, serotonin (5-hydroxytryptamine) and kinins (basic peptides), concentrated in cytoplasmic granules. Contact of the IgE antibodies, which are fixed to mast cells and basophils, with antigens can trigger cross-linking of the IgE antibodies. In turn, this cross-linking causes degranulation of mast cells and basophils, which releases the chemical mediators and produces manifestations of the allergic response, eg., bronchial asthma referred to earlier. In order to reduce the undesirable allergic responses, it has been suggested in the prior art to administer various compounds which have an antiallergic characteristic of interfering with the degranulation of mast cells and basophils. There is a need for such antiallergic compounds having increased efficacy over known compounds.
2. Description of the Prior Art
Japanese Patent Publication No. 52.039677 (KOWA) describes xanthene derivatives which are useful as anti-allergic agents or in drugs for treating asthma. The compounds disclosed have the formula: ##STR2## in which R is hydrogen, lower alkyl, hydroxy, lower alkoxy, hydroalkoxy, halogen or trifluoromethyl. R' is hydrogen or lower alkyl.
KOWA discloses that the xanthene compounds are produced by dehydrogenation of the corresponding tetrahydroxanthene compounds. These intermediate tetrahydroxanthene compounds have the structure: ##STR3## wherein R and R' are defined as above. The intermediates are disclosed by KOWA as having "antiinflammatory, antiallergic and blood sugar lowering activities." All of the tetrahydroxanthenes disclosed by KOWA have a COOR' substitutent at the 2-position and, if substituted at the 6, 7 or 8-position, have an --OH; --OCH.sub.3 ; --O--C.sub.2 H.sub.4 --OH; --Cl, --CH.sub.3 or --CF.sub.3 present. There is no disclosure or suggestion that the 2-position can be substituted with an alkyl chain or disubstituted; that the oxygen atom in the 10-position can be replaced by --S, or --SO.sub.2 ; or that R can be carboxyl, alkylthio, alkylsulfonyl, alkylsulfinyl, alkoxycarbonyl or tetrazolyl.